The receptive fields of neurons in layer 4 of the ferret and cat striate cortex are oriented, rectangular and frequently end-inhibited as well. this complexity stands in marked contrast to the receptive fields of cells one synapse away in the lateral geniculate nucleus, which have a circular, center-surround organization. The long-term goal of the project described here is to investigate the synaptic physiology of characteristic pathways in striate cortex to understand, stepwise, how sensory input is restructured by the synapses it traverses. In 1965, Hubel and Wiesel proposed a model circuit for the response property of end-stopping. They suggested that cells with long receptive fields might overlap the end-stopped regions and suppress activity there. Over the intervening decades, the results of anatomical investigations and extracellular recordings made in vivo have led to a more detailed formulation of the original hypothesis. current theory holds that end- stopping in layer 4 is relayed from layer 6 through a disynaptic inhibitory connection. The specific identity and connectivity of the cells providing the inhibition remain to be established. A central prediction of this hypothesis is that the activation of layer 6 should have a net inhibitory effect on synaptic events driven by geniculocortical inputs for cells corresponding to those which are end- inhibited. Whole-cell recordings from brain slices will be made to test this prediction. Specifically, the responses to activation of the thalamic and interlaminar pathways alone as well as together will be compared for single cells in layer 4. All cells will be labelled intracellularly to allow correlation between physiology and anatomy. When necessary, recordings will be made from neurons that are visually identified prior to study in order to ensure that information about key minority populations such as inhibitory cells is acquired. Pathway- specific integration will then be examined at a finer grain by analyzing the unitary response provided from one cell to the next at each major synaptic station along the thalamic and interlaminar circuits. A knowledge of how the brain operates in the everyday situation provides a standard against which to judge changes that occur in the course of various disorders as well as a model system on which to test drugs developed to treat illness. From this perspective, the visual cortex is an obvious site to study; its function and anatomy are better understood than any other cortical region. A deeper understanding of synaptic mechanisms provides insight into the processes that go awry during disease. The work proposed here bears directly on a central theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing.